The objectives of this project are (1) to detect natural and induced mutations in mice, (2) to achieve understanding of the molecular events occurring in the process of mutation induction, and (3) to relate these events to the life, form and function of the mammalian organism. Our project is relevant to the problem of human exposures to environmental chemicals; particularly, the increased risk of genetic disease in the offspring of exposed individuals. We have detected a variety of mutations at specific biochemical loci with electrophoretic methods, characterized several normal and mutant genes (and gene products), and examined the offspring of mutagen-treated and control parents for the physical manifestation of polygenic mutations affecting the skeleton. Recently, we identified a group of highly variable animals produced from ethylnitrosourea-treated males. We analyzed the variability to distinguish abnormalities of both size and shape. The experiment involved over 300,000 quantitative measurements on 12 bones from about 1,000 mice. The animals showing the effect were produced immediately after the male parents recovered from a period of sterility induced by the chemical. All twelve of the bones examined were affected. The progeny from matings that took place before the sterile period were normal. The progeny from much later matings were also normal. Virtually all offspring in the one treatment group were affected, and the expression of the variability was different in each individual. The results suggest that children may show abnormal growth and development under conditions of parental male exposure like those in our experiment. Although we studied only the skeleton, it would be reasonable to suspect that other structures and functions were also damaged.